Low-intensity pulsed ultrasound attenuates atrial remodeling and atrial fibrillation after myocardial infarction: an experimental pre-clinical study.

Aims: Post-infarct atrial remodeling creates a substrate for atrial fibrillation (AF), yet no cardiac-specific, non-invasive therapy targets this process. Low-intensity pulsed ultrasound (LIPUS) limits ventricular remodeling in pre-clinical models, but its impact on atrial remodeling and AF after myocardial infarction (MI) is unknown.

Methods and results: MI was induced in rats by surgical ligation of the left coronary artery, whereas a separate AF rat model was created by daily tail-vein injections of acetylcholine/CaCl₂ for 28 days. LIPUS treatment did not cause significant structural, functional or electrophysiological changes in the atrial tissue of healthy rats. In MI rats, LIPUS markedly attenuated atrial electrical remodeling, fibrosis, and inflammation, thereby reducing AF susceptibility. Transcriptomic analysis demonstrated a potential role of Adam19/TGF-β/Smad2/3 signaling in response to LIPUS treatment, whereas activation of Adam19/TGF-β/Smad2/3 signaling worsened fibrosis, and abolished the anti-arrhythmic benefit of LIPUS. Similar antifibrotic and antiarrhythmic effects were reproduced in the acetylcholine/CaCl₂ AF model, underscoring LIPUS as a promising non-invasive approach to attenuate AF after MI.

Conclusions: In preclinical post-MI models, LIPUS attenuated atrial structural and electrical remodeling and lowered AF susceptibility, plausibly via modulation of an Adam19/TGF-β/Smad2/3 signaling cascade. These findings are promising but preliminary; priorities include determining whether the atrial effects are direct or secondary to ventricular remodeling and altered hemodynamics, confirming mechanisms across models, defining dose-response and safety, and validating efficacy and translational relevance in large-animal studies and early-phase trials before any clinical application.